Conservative Peri-Procedural Anticoagulation Management in Patients with Venous Thromboembolic Disease Results in a Low Proportion of Thrombosis and Bleeding

Abstract 546

The optimal strategy for peri-procedural warfarin management in patients with venous thromboembolic disease (VTE) is unknown because most studies to date have included small proportions of VTE patients. Guidelines are largely based on expert opinion and recommend low-molecular-weight heparin (LMWH) bridging in patients at high or moderate risk for VTE. LMWH bridging may be associated with an increased bleeding risk, which if occurs, would result in temporary cessation of anticoagulation (AC) potentially leading to a paradoxical increased thrombotic risk. We conducted a single-center retrospective cohort study to examine the effectiveness of conservative peri-procedural AC management in VTE (DVT or PE) patients.

We included all patients from our institution's thrombosis unit between 1993 and 2011 who required peri-procedural AC management for planned procedures. The thrombosis unit has, on average, 800 patients on chronic AC for VTE. Patients were excluded if they had other indications for AC, had an acute VTE <90 days before the procedure, or had no follow-up after the procedure. Our centre uses a conservative bridging strategy in these patients consisting of holding warfarin 5 days before the procedure without administering LMWH. Postoperatively all patients resume warfarin as soon as they can swallow. For ambulatory procedures no LMWH is given after the procedure, whereas patients undergoing in-hospital procedures are usually given prophylactic LMWH starting the morning after surgery until discharge or when the INR is therapeutic, whichever occurs first. The primary outcome was incidence of VTE within 90 days of the procedure. Secondary outcomes were 90-day incidence of major and total bleeding and all-cause mortality. Confidence intervals for proportions were calculated using the Wilson's score method. Groups were compared using χ² or Fisher's exact tests. Survival analysis was done using the Kaplan-Meier method. Two-sided p values ≤0.05 were considered statistically significant.

During the study period there were 634 procedures in 416 patients (47.4% males). The mean age was 64.9 years (SD 15.8) and 79.1% of patients had idiopathic VTE. There were 156 procedures (24.6%) completed in-hospital. Pre- and post-procedure bridging was used in 15 (2.4%) and 153 (24.1%) procedures, respectively. The 90-day cumulative incidence of VTE was 0.63% (95% CI 0.25–1.61). The VTE events were 4 DVTs (postoperative day 3, 29, 41, 43) with no associated mortality. The 90-day cumulative incidence of major and total bleeding events was 1.58% (95% CI 0.86–2.88) and 3.47% (95% CI 2.30–5.20), respectively. All-cause mortality rate was 0.63% (95% CI 0.25–1.61); one patient died from a myocardial infarction 3 days after an abdominal aortic aneurysm repair, a second died from an ischemic stroke the morning of a colonoscopy and 2 patients had non-VTE related deaths.

The effects of type of procedure and use of bridging on outcomes are shown in Table 1. The use of pre- or post-procedure bridging was not associated with VTE or bleeding. There were significantly more total bleeding events with inpatient procedures. There was a significant correlation between bleeding and VTE events: 13.6% of patients with any bleeding and 30% with major bleeding developed a VTE complication compared with 0.2% of those without bleeding. Spearman's correlation coefficients were 0.311 and 0.470, respectively (p<0.001). Two postoperative DVTs (50%) developed after warfarin was held for an extended period of time (1 major bleed, 1 neurosurgical complication).

Conservative peri-procedural AC management in VTE patients on warfarin for at least 3 months results in a low risk of thrombotic and bleeding events. A randomized controlled trial in chronically anticoagulated VTE patients is needed to provide definitive conclusions but a conservative approach appears promising.